1,3-Dibromo-5,5-dimethylhydantoin → Tert-butyl 3-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)piperidine-1-carboxylate

HRID 1972735Notes

Reaction equation

[NH2:1][C:2]1[C:7]2=[CH:8][CH:9]=[C:10]([CH:11]3[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.[Br:24]N1C(C)(C)C(=O)N(Br)C1=O>CN(C=O)C.C(O)(=O)C>[NH2:1][C:2]1[C:7]2=[C:8]([Br:24])[CH:9]=[C:10]([CH:11]3[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: -20 °C

Procedure

To a cooled (−20° C.) solution tert-butyl 3-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)piperidine-1-carboxylate (891 mg, 2.81 mmol) in DMF (8.7 mL) and acetic acid (7.0 mL) was added 1,3-dibromo-5,5-dimethylhydantoin (401 mg, 1.40 mmol) in 3 portions over 10 min. The mixture was allowed to stir at −20° C. for 90 min. The reaction was quenched with the addition 5% aqueous K2CO3 (20 mL) and was allowed to warm to rt. The mixture was extracted with ethyl acetate (3×20 mL). The combined organics were washed with brine, dried (Na2SO4) and evaporated to provide 1.07 g (96%) of the desired product. ES-MS m/z 396.06 [M+H]+, HPLC RT (min) 3.05.

Workup

customThe reaction was quenched with the addition 5% aqueous K2CO3 (20 mL)
temperatureto warm to rt
extractionThe mixture was extracted with ethyl acetate (3×20 mL)
washThe combined organics were washed with brine
dry with materialdried (Na2SO4)
customevaporated

Sources & evidence

ORD record: ord-7b017ac9aa9145e5ab359032d0278611
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431695B2

Reaction notes

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